Genome-Wide Analysis of DNA Methylation and Cigarette Smoking in a Chinese Population

Background: Smoking is a risk factor for many human diseases. DNA methylation has been related to smoking, but genome-wide methylation data for smoking in Chinese populations is limited. Objectives: We aimed to investigate epigenome-wide methylation in relation to smoking in a Chinese population. Methods: We measured the methylation levels at > 485,000 CpG sites (CpGs) in DNA from leukocytes using a methylation array and conducted a genome-wide meta-analysis of DNA methylation and smoking in a total of 596 Chinese participants. We further evaluated the associations of smoking-related CpGs with internal polycyclic aromatic hydrocarbon (PAH) biomarkers and their correlations with the expression of corresponding genes. Results: We identified 318 CpGs whose methylation levels were associated with smoking at a genome-wide significance level (false discovery rate < 0.05), among which 161 CpGs annotated to 123 genes were not associated with smoking in recent studies of Europeans and African Americans. Of these smoking-related CpGs, methylation levels at 80 CpGs showed significant correlations with the expression of corresponding genes (including RUNX3, IL6R, PTAFR, ANKRD11, CEP135 and CDH23), and methylation at 15 CpGs was significantly associated with urinary 2-hydroxynaphthalene, the most representative internal monohydroxy-PAH biomarker for smoking. Conclusion: We identified DNA methylation markers associated with smoking in a Chinese population, including some markers that were also correlated with gene expression. Exposure to naphthalene, a byproduct of tobacco smoke, may contribute to smoking-related methylation. Citation: Zhu X, Li J, Deng S, Yu K, Liu X, Deng Q, Sun H, Zhang X, He M, Guo H, Chen W, Yuan J, Zhang B, Kuang D, He X, Bai Y, Han X, Liu B, Li X, Yang L, Jiang H, Zhang Y, Hu J, Cheng L, Luo X, Mei W, Zhou Z, Sun S, Zhang L, Liu C, Guo Y, Zhang Z, Hu FB, Liang L, Wu T. 2016. Genome-wide analysis of DNA methylation and cigarette smoking in Chinese. Environ Health Perspect 124:966–973; http://dx.doi.org/10.1289/ehp.150983

Physical activity attenuates the associations of systemic immune-inflammation index with total and cause-specific mortality among middle-aged and older populations

Abstract Systemic immune-inflammation index (SII) emerged as a biomarker of chronic inflammation and an independent prognostic factor for many cancers. We aimed to investigate the associations of SII level with total and cause-specific mortality risks in the general populations, and the potential modification effects of lifestyle-related factors on the above associations. In this study, we included 30,521 subjects from the Dongfeng-Tongji (DFTJ) cohort and 25,761 subjects from the National Health and Nutrition Examination Survey (NHANES) 1999–2014. Cox proportional hazards regression models were used to estimate the associations of SII with mortality from all-cause, cardiovascular diseases (CVD), cancer and other causes. In the DFTJ cohort, compared to subjects in the low SII subgroup, those within the middle and high SII subgroups had increased risks of total mortality [hazard ratio, HR (95% confidence interval, CI) = 1.12 (1.03–1.22) and 1.26 (1.16–1.36), respectively) and CVD mortality [HR (95%CI) = 1.36 (1.19–1.55) and 1.50 (1.32–1.71), respectively]; those within the high SII subgroup had a higher risk of other causes mortality [HR (95%CI) = 1.28 (1.09–1.49)]. In the NHANES 1999–2014, subjects in the high SII subgroup had higher risks of total, CVD, cancer and other causes mortality [HR (95%CI) = 1.38 (1.27–1.49), 1.33 (1.11–1.59), 1.22 (1.04–1.45) and 1.47 (1.32–1.63), respectively]. For subjects with a high level of SII, physical activity could attenuate a separate 30% and 32% risk of total and CVD mortality in the DFTJ cohort, and a separate 41% and 59% risk of total and CVD mortality in the NHANES 1999–2014. Our study suggested high SII level may increase total and CVD mortality in the general populations and physical activity exerted a beneficial effect on the above associations

Essential Metals Zinc, Selenium, and Strontium Protect against Chromosome Damage Caused by Polycyclic Aromatic Hydrocarbons Exposure

Essential metals play important roles in maintaining cellular homeostasis, but the effects of their interaction with the environmental pollutants are still not very well-known in human subjects. The aim of this study was to evaluate the roles of essential metals and their interactions with polycyclic aromatic hydrocarbons (PAHs) on chromosome damage, an early carcinogenic event. A total of 1245 male workers were included in this study and the levels of 11 urinary essential metals, 12 urinary PAH metabolites, plasma concentrations of benzo­[a]­pyrene-r-7,t-8,t-9,c-10-tetrahydotetrol-albumin (BPDE-Alb) adducts, and lymphocyte micronucleus (MN) frequencies were monitored. We found that zinc (Zn), selenium (Se), and strontium (Sr) have significant inverse dose–response relationships with MN frequencies (all <i>P</i> < 0.05). Furthermore, the protective roles of Zn, Se, and Sr were mainly shown among subjects with high levels of BPDE-Alb adducts. Significant effect modification of BPDE-Alb adducts on the associations of Zn, Se, and Sr with MN frequencies was observed (all <i>P</i>_interaction < 0.05). Our study showed evidence that Zn, Se, and Sr play protective roles in reducing chromosome damage, and these effects can be modified by PAH exposure levels. These findings add potential evidence for the preventive effects of Zn, Se, and Sr against carcinogenesis in human subjects

Association of shift-work, daytime napping, and nighttime sleep with cancer incidence and cancer-caused mortality in Dongfeng-tongji cohort study

<p><b>Background:</b> Few studies investigated the combined effects of night-shift work, daytime napping, and nighttime sleep on cancer incidence and mortality.</p> <p><b>Methods:</b> A total of 25,377 participants were included in this study. Information on sleep habits, cancer incidences, and mortalities were collected. Cox proportional hazards models were used to calculate the adjusted hazard ratios and 95% confidence intervals (HRs, 95%CIs).</p> <p><b>Results:</b> Male subjects experienced ≥20 years of night-shift work, or without daytime napping had an increased risk of cancer, when compared with males who did not have night-shift work or napped for 1–30 min [HR (95%CI) = 1.27 (1.01–1.59) and 2.03 (1.01–4.13), respectively]. Nighttime sleep for ≥10 h was associated with a separate 40% and 59% increased risk of cancer [HR (95%CI) = 1.40 (1.04–1.88)] and cancer-caused mortality [HR (95%CI) = 1.59 (1.01–2.49)] than sleep for 7–8 h/night. Combined effects of three sleep habits were further identified. Male participants with at least two above risk sleep habits had a 43% increased risk of cancer [HR (95%CI) = 1.43 (1.07–2.01)] and a 2.07-fold increased cancer-caused mortality [HR (95%CI) = 2.07 (1.25–3.29)] than those who did not have any above risk sleep habits. However, no significant associations were observed among women.</p> <p><b>Conclusions:</b> Long night-shift work history, without daytime napping, and long nighttime sleep duration were independently and jointly associated with higher cancer incidence among males.KEY MESSAGES</p><p>Night-shift work of ≥20 years, without napping, and nighttime sleep of ≥10 h were associated with increased cancer incidence.</p><p>Nighttime sleep ≥10 h was associated with a 2.07-fold increased cancer-caused mortality among males.</p><p>Combined effects of night-shift work ≥20 years, without napping, and nighttime sleep ≥10 h on increasing cancer incidence were existed among males.</p><p></p> <p>Night-shift work of ≥20 years, without napping, and nighttime sleep of ≥10 h were associated with increased cancer incidence.</p> <p>Nighttime sleep ≥10 h was associated with a 2.07-fold increased cancer-caused mortality among males.</p> <p>Combined effects of night-shift work ≥20 years, without napping, and nighttime sleep ≥10 h on increasing cancer incidence were existed among males.</p